Confo Therapeutics: Drugging the Undruggable

Llama single-domain antibodies have found yet another application, one that Confo Therapeutics is fully exploiting. Ablynx is developing Nanobodies®, AgroSavfe focuses on Agrobodies®, and Confo will now use its Confobodies to lock G-protein coupled receptors (GPCRs) into position. This enables the company to screen for small molecules targeting specific GPCR conformations, a most innovative approach to GPCR drug development!

GPCRs are a huge family of protein receptors. They are present on all cell types and are involved in numerous biological processes and diseases. Metabolism, cell growth, inflammation and immunity, neurotransmission, behavior: all are regulated by GPCRs. For this reason, the receptors are extremely popular drug targets. Approximately 30% of all existing drugs target GPCRs, amounting to tens of billions of dollars in annual revenue.

Currently, GPCR-targeting drugs are mostly antagonists, drugs that block GPCR signaling. In some diseases, however, a stimulatory therapy is needed to restore natural signaling. Unfortunately, developing small molecule GPCR-stimulating drugs, or agonists, has proven to be a huge challenge.

Freeze ’em, scan ’em, drug ’em

One VIB startup company now has the means to revolutionize GPCR drug discovery: Confo Therapeutics. The key element in the company’s technology? Llama single-domain antibodies. These became famous when Confo’s older brother Ablynx started to use them as therapeutics, calling them Nanobodies. Confo Therapeutics deploys its “Confobodies” in a very different way.

“GPCRs are incredibly flexible,” explains Cedric Ververken, CEO at Confo and former Vice President of Business Development at Ablynx. “Depending on their different shapes or conformations, different signaling pathways in the cell can be activated. The trick is to specifically activate the pathway of your therapeutic interest. By using single-domain antibodies from llama’s, or Confobodies as we call them, we can stabilize the GPCR in the desired conformation. Once we have achieved this, the frozen GPCR is used to screen small molecules for therapeutic effects.”

A practical example is the opioid receptor, a frequently used target to relieve pain. The use of opioids, such as morphine, is associated with a range of side effects, including constipation, respiratory distress and addiction. This is because these compounds activate multiple signaling pathways through the receptor. Confo can now use its technology to identify and freeze the state of the opioid receptor responsible for pain alleviation, and develop drugs that are specific for this conformation, eliminating side effects.

From technology platform to drug discovery company

As such, Confo Therapeutics owns an incredibly versatile technology platform. Of course it’s impossible for a start up to explore the entire range of possibilities of the platform because of restrictions on resources. So how does Confo pick the targets it wants to pursue? Ververken sheds light on the company’s portfolio strategy:

“First of all, we analyze where the technology has the most to offer. In which diseases or targets have traditional methods failed, and can we offer a solution? Secondly, we spread our risk. Only going after unknown or poorly characterized targets is incredibly risky. A last factor is the starting points we have from our lab of origin, the lab of prof. Steyaert at the VUB. We know that we can generate candidate drugs to those targets much faster than if we would start all over with completely new targets. Our portfolio is a healthy mix of known GPCRs where our technology can make a difference and new targets where we can do something truly innovative.”

In addition to a highly innovative technology platform, Confo Therapeutics is led and supported by an impressive team. As an expert in structural biology, founder Prof. Steyaert consults as scientific advisor to the company. Co-founder Toon Laeremans, Head of Technology, specialized in generating single-domain antibodies, and has years of experience at Ablynx and in the Steyaert lab, where the Nanobodies were initially discovered and where the Confo Technology was established. To bring drug discovery and development experience into the team, Confo was able to attract another A-list talent: Galapagos veteran Christel Menet. Menet led the discovery of Galapagos’ flagship molecule, filgotinib, and was appointed CSO at Confo. Moreover, CEO Ververken has more than 10 years of experience in both R&D and business development at Ablynx. It seems like this technology is in good hands!

The Venture Capitalist’s view

V-Bio Ventures was in contact with Confo since day one and has invested upon the first closing of the fund end 2015, when it joined the initial investors syndicate formed by Capricorn, QBic and SOFI, with additional investors VIB, MINTS (University of Michigan) and PMV. V-Bio Ventures holds an unshakable belief in the company’s potential:

“Confo’s profile is right up our alley. The company owns a breakthrough technology, which is broadly endorsed by the scientific community. By enabling drug development for previously undruggable targets, they bring significant added value to the already huge market of GPCR-targeting medicines.

We’re also convinced that the company employs a solid strategy to capture the value of the technology platform: building a pipeline of proprietary projects on the one hand and starting strategic collaborations with partners on the other hand.

Together with the management, we have developed a clear vision of the company’s trajectory and future, and we’re confident that the team behind Confo is more than able to make it a very bright future.”

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